This is an Exploratory/Developmental grant application whose goal is to advance diffusion tensor magnetic resonance (DT-MR) imaging studies of spinal cord injury. There is abundant evidence that the diffusion characteristics of the cord white matter reflect the presence and integrity of axons. In order to make reliable decisions concerning the abnormality of a measurement derived from the DT, the variation of that measurement must be properly characterized over both normal and afflicted populations. The proposed methods for registration and spatial normalization of DT data will enable quantitative characterizations of the variation of measurements over both selected population groups and single-subject longitudinal studies to assist disease diagnosis or treatment monitoring. In particular, the long-term aim is to determine those DTMR characteristics, which predict the severity of initial axonal damage, subsequent degeneration and the extent of regeneration in injured spinal cord. Specific aims for this proposal are as follows:1.To develop a method for non-rigid registration and spatial normalization of DT-MR images. There are two issues of concern when adapting existing registration algorithms to work with DT-MR data: first, we require a measure of image similarity to drive the registration process, and, second, we need to consider the effects of normalizing transformations on the voxel data in a DT image-DTs contain orientational information that must be handled appropriately when transformations are applied. The proposed project will investigate both of these issues.2.To characterize the DT-MR registration algorithm over synthetic data. We will use numerical phantoms, for which perfect ground truth data is readily available, to systematically evaluate the performance of the proposed registration method under different (a) noise levels, (b) spatial resolutions and (c) degrees of shape disparity.3.To validate the DT-MR registration algorithm over lamprey spinal cord data. We will validate the proposed method by registering DT-MR studies of lamprey spinal cord, imaged in different configurations. DT-MRIs of the lamprey spinal cord would be ideal for evaluating the developed method, since lamprey anatomy allows the spinal cord to undergo non-rigid transformations. Moreover, the lamprey cord contains a number of "giant" axons, which can be resolved by high resolution MR imaging. This permits direct observation of the distribution and course of the giant axons, with MR imaging, but independent of diffusion studies. Thus, this direct observation offers a method to test registration accuracy without resorting to maneuvers such as histological study of the cord, which might distort the anatomy.